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Chimeric antigen receptor T cells targeting FcRH5 provide robust tumour-specific responses in murine xenograft models of multiple myeloma

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Listed:
  • Dongpeng Jiang

    (The First Affiliated Hospital of Soochow University, Collaborative Innovation Center of Hematology, Soochow University)

  • Haiwen Huang

    (The First Affiliated Hospital of Soochow University)

  • Huimin Qin

    (The First Affiliated Hospital of Soochow University, Collaborative Innovation Center of Hematology, Soochow University)

  • Koukou Tang

    (The First Affiliated Hospital of Soochow University, Collaborative Innovation Center of Hematology, Soochow University)

  • Xiangru Shi

    (The First Affiliated Hospital of Soochow University, Collaborative Innovation Center of Hematology, Soochow University)

  • Tingting Zhu

    (The First Affiliated Hospital of Soochow University, Collaborative Innovation Center of Hematology, Soochow University)

  • Yuqing Gao

    (The First Affiliated Hospital of Soochow University, Collaborative Innovation Center of Hematology, Soochow University)

  • Ying Zhang

    (The First Affiliated Hospital of Soochow University, Collaborative Innovation Center of Hematology, Soochow University)

  • Xiaopeng Tian

    (The First Affiliated Hospital of Soochow University)

  • Jianhong Fu

    (The First Affiliated Hospital of Soochow University)

  • Weiwei Qu

    (The First Affiliated Hospital of Soochow University, Collaborative Innovation Center of Hematology, Soochow University)

  • Weilan Cai

    (The First Affiliated Hospital of Soochow University, Collaborative Innovation Center of Hematology, Soochow University)

  • Yang Xu

    (The First Affiliated Hospital of Soochow University, Collaborative Innovation Center of Hematology, Soochow University)

  • Depei Wu

    (The First Affiliated Hospital of Soochow University, Collaborative Innovation Center of Hematology, Soochow University)

  • Jianhong Chu

    (The First Affiliated Hospital of Soochow University, Collaborative Innovation Center of Hematology, Soochow University)

Abstract

BCMA-targeting chimeric antigen receptor (CAR) T cell therapy demonstrates impressive clinical response in multiple myeloma (MM). However, some patients with BCMA-deficient tumours cannot benefit from this therapy, and others can experience BCMA antigen loss leading to relapse, thus necessitating the identification of additional CAR-T targets. Here, we show that FcRH5 is expressed on multiple myeloma cells and can be targeted with CAR-T cells. FcRH5 CAR-T cells elicited antigen-specific activation, cytokine secretion and cytotoxicity against MM cells. Moreover, FcRH5 CAR-T cells exhibited robust tumoricidal efficacy in murine xenograft models, including one deficient in BCMA expression. We also show that different forms of soluble FcRH5 can interfere with the efficacy of FcRH5 CAR-T cells. Lastly, FcRH5/BCMA-bispecific CAR-T cells efficiently recognized MM cells expressing FcRH5 and/or BCMA and displayed improved efficacy, compared with mono-specific CAR-T cells in vivo. These findings suggest that targeting FcRH5 with CAR-T cells may represent a promising therapeutic avenue for MM.

Suggested Citation

  • Dongpeng Jiang & Haiwen Huang & Huimin Qin & Koukou Tang & Xiangru Shi & Tingting Zhu & Yuqing Gao & Ying Zhang & Xiaopeng Tian & Jianhong Fu & Weiwei Qu & Weilan Cai & Yang Xu & Depei Wu & Jianhong C, 2023. "Chimeric antigen receptor T cells targeting FcRH5 provide robust tumour-specific responses in murine xenograft models of multiple myeloma," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39395-4
    DOI: 10.1038/s41467-023-39395-4
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    References listed on IDEAS

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    1. Mehmet Kemal Samur & Mariateresa Fulciniti & Anil Aktas Samur & Abdul Hamid Bazarbachi & Yu-Tzu Tai & Rao Prabhala & Alejandro Alonso & Adam S. Sperling & Timothy Campbell & Fabio Petrocca & Kristen H, 2021. "Biallelic loss of BCMA as a resistance mechanism to CAR T cell therapy in a patient with multiple myeloma," Nature Communications, Nature, vol. 12(1), pages 1-7, December.
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